(1) Field of the Invention
This invention relates to a process for the preparation of uracils. More specifically, it relates to a process for the preparation of uracil and 5-alkyluracils.
(2) Description of the Prior Art
Uracils are important constituents of nucleic acids and are valuable as starting compounds for the preparation of medicines. 5-Methyluracil, which is one of 5-alkyluracils, is called "thymine" and is an important constituent of nucleic acids. Furthermore, thymine and other 5-alkyluracils are important as starting materials for the preparation of medicines. For example, when uracil is fluorinated, 5-fluorouracil (hereinafter referred to as "5-FU") having a carcinostatic action can be obtained, and it is well known that "Futoraful," which is a famous carcinostatic agent, can be prepared by using 5-FU as a starting material. It is also known that Idoxuridine, which is a famous antiviral agent, is prepared by using uracil as a starting compound.
Since uracil is valuable as a starting material for the preparation of various medicines as described above, various investigations have been made on the process for preparing uracil. As one known process for the preparation of uracil, the process disclosed in Tetrahedron Letters, 27, 2321-2322 (1976), which comprises heating and reacting propiolic acid (CH.tbd.CCOOH) with urea in polyphosphoric acid to form uracil can be mentioned. However, the carboxylic acid used as the starting material is expensive and since the addition of water to the liquid reaction mixture after completion of the reaction is necessary to precipitate uracil, polyphosphoric acid used in a large quantity is difficult to recover for repeated use thereof.
Another known process for the preparation of uracil is the process disclosed in Trans. Science Soc. China, 8, 83-84 (1934), which comprises reacting malic acid with urea in a large quantity of fuming sulfuric acid. This process, however, is defective in that a large quantity of fuming sulfuric acid should be used and since the addition of a large amount of water to the liquid reaction mixture after completion of the reaction is necessary to precipitate uracil, urea and fuming sulfuric acid used for the reaction are difficult to recover for repeated use thereof.
Many processes for the preparation of uracil, other than those mentioned above, are known, but these processes are not satisfactory in that expensive starting materials should be used or the steps are complicated.